A new Hypoxic Ischemic Encephalopathy model in neonatal rats

Abstract

Background Hypoxic-Ischemic Encephalopathy (HIE) occurs when an infant's brain does not receive adequate blood and oxygen supply, resulting in ischemic and hypoxic brain damage during delivery. Currently, supportive care and hypothermia have been the standard treatment for HIE. However, there are still a 20% mortality and most of the survivors are associated with significant neurodevelopmental disability. HIE animal model was first established by Vannucci et al., in 1981, and has been used extensively to explore the mechanisms of brain damage and its potential treatment. The Vannucci model involves the unilateral common carotid artery occlusion followed by 90 min hypoxia (8% oxygen). The purpose of this study is to define and validate a modified HIE model which mimics closely that of the human neonatal HIE. Method The classic Vannucci HIE model occludes one common carotid artery followed by 90 min hypoxia. In the new model, common carotid arteries were occluded bilaterally followed by breathing 8% oxygen in a hypoxic chamber for 90, 60 and 30 min, followed by the release of the common carotid artery ligatures, mimicking a reperfusion. Result We studied 110 neonatal rats in detail, following the modified in comparison with the classical Vannucci models. The classical Vannucci model has a consistent surgical mortality of 18% and the new modified models have a 20%–46%. While mortality depended on the duration of hypoxia, fifty-two animals survived for behavioral assessments and standard histology. The modified HIE model with 60 min of transient carotid occlusion is associated with a moderate brain damage, and has a 30% surgical mortality. This modified experimental model is regarded closer to the human situation than the classical Vannucci model.

Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia

“…The neonatal rats were un-sexed chosen, of which 42% were female. The mortality of HIE was 30% which is consist with our previous study ( Lyu et al, 2021 ), and similar with the human situation ( Shankaran et al, 2005 ). A total of 230 animals survived the HIE.…”

“…Other important aspects such as brain water content, brain atrophy and angiogenesis were not investigated. Apoptosis and necrosis were assessed early ( Lyu et al, 2021 ) but not long term. A systematic motor, learning and memory tests were not planned in this study.…”

“…The HIE model involves the ligation of one common carotid artery followed by hypoxia (8% oxygen), however, this model did not simulate the real situation of human HIE. In this study, we used a modified bilateral temporary occlusion HIE animal model as we described recently, which better mimics the human situation of a difficult labor ( Lyu et al, 2021 ). All animal experimentation protocols followed the guidelines for the care and use of animals and were approved by the ethics committee of the Chinese University of Hong Kong.…”

“…However, several aspects of HUCB as a treatment for HIE remain unclear, including the mechanisms of its therapeutic effects, the cell types that contribute the most to this effect and the optimal cell transplantation route, number of cells and timing of transplantation. Therefore, in this study, we investigated the effects of transplantation with total HUCB and its two components, mononuclear cells (MNCs) and the red cell fraction (RCF), over the short term (7 days after cell transplantation) and long term (1 and 3 months after cell transplantation) in a modified HIE rat model ( Lyu et al, 2021 ).…”

Ambient Temperature Is Correlated With the Severity of Neonatal Hypoxic-Ischemic Brain Injury via Microglial Accumulation in Mice

“…However, quite meaningful results were obtained despite using P9-10 mice, which may suggest the ambient temperature affects much more than the 1-day growth. In contrast, as previously reported, we should focus not only on differences of animals but also on the composition of the procedures during hypoxic exposure as oxygen concentration and exposure time (38,44,45). By strictly controlling the ambient temperature, severity could be reproduced at various levels as same as the arrangement of oxygen concentration and hypoxic exposure time.…”